Osteoporotic bone represents – particularly in case of fractures – difficult conditions for its regeneration. The increased activity of osteoclasts in case of high turnover osteoporosis leads to slow fracture healing. To treat bone defects under these conditions, we focused on a degradable material of gelatin-modified calcium and strontium phosphates. The material is ought to release strontium ions and keep the cation concentration on a physiological level, to stimulate osteoblastogenesis either direct by ion release or indirect after material resorption by osteoclasts.
A phosphate solution was used to prestructure gelatin, which was mixed afterwards with calcium and/or strontium containing solutions. The precipitated organically modified mineral was cross-linked and lyophilized to obtain porous 3D samples. The resulting material was investigated according to ion release and degradability. Subsequently, cell culture of human mesenchymal stromal cells (hBMSC) as well as human monocytes was performed in vitro. Finally, the material was implanted in a femoral defect in osteoporotic rats.
The materials in this study caused an initial ion release in calcium-rich (2.0 mM) and low-calcium (0.4 mM) minimum essential medium. The cultivation of monocytes next to the material led to formation of osteoclast-like cells, able to migrate, fuse, and differentiate in case of gelatin-modified calcium / strontium phosphate with a Ca/Sr-ratio of 5:5. Osteoclastogenesis was proved morphologically and by PCR. Pure gelatin-modified strontium phosphate affected osteoclast formation. The osteoblastic reaction of hBMSC was most significant with mixed Ca/Sr-phosphates as well. Mass spectroscopy (ToF-SIMS) of thin cuts of the rat femurs revealed an increased bone formation with increasing strontium in the material, supported by histological analysis. The study showed, that an adjustment of bone substitute materials – with respect to its degradation and ion release – to demands of systemically altered bone is possible.